Is CLIP1 p.Ile1237Leu (c.3709A>T) pathogenic?

CLIP1 p.Ile1237Leu (c.3709A>T) is classified Uncertain significance in CLIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-06). AlphaMissense: likely benign (0.0898); Absent from gnomAD v4.1.

How common is CLIP1 p.Ile1237Leu (c.3709A>T) in the general population?

CLIP1 p.Ile1237Leu (c.3709A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLIP1 p.Ile1237Leu (c.3709A>T)?

AlphaMissense predicts likely benign (score 0.0898) — an in-silico prediction, not a clinical call.

CLIP1 p.Ile1237Leu

c.3709A>T · rs1566069686 · VCV1336583

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0898 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0898	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -5.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP 0.84, phastCons 0.013
Regional constraint	o/e 0.84	unconstrained · MANE · 78 kb · p 3e-08 · regional, not allelic
Overall
CADD	13.89	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLIP1
Protein: p.Ile1237Leu
Coding: c.3709A>T
MANE Select: NM_001247997
dbSNP: rs1566069686
Type: single nucleotide variant
Location: chr12:122279084 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.16 · 11 PDB

Full CLIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLIP1 p.Ala142Val Uncertain significance ★★ ⚠ same type
CLIP1 p.Arg342Cys Uncertain significance ★★ ⚠ same type
CLIP1 p.Gly1356Arg Uncertain significance ★★ ⚠ same type
CLIP1 p.Lys1267Arg Uncertain significance ★★ ⚠ same type
CLIP1 p.Ala1224Ser Likely benign ★★ same type
CLIP1 p.Ala301= Benign ★★ same type
CLIP1 p.Asn99= Benign/Likely benign ★★ same type
CLIP1 p.Lys851= Likely benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/clip1-p-ile1237leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown